METHOD DEVELOPMENT AND VALIDATION OF FAST DISSOLVING TABLET OF RAMIPRIL BY HPLC METHOD

Objective: The Objective of present work is method development and validation of HPLC method for the quantitation of Ramipril in Fast dissolving tablet (FDT).Methods: A stable, linear, rapid, accurate and selective HPLC method has been developed for the quantification of Ramipril in FDT using buffer and acetonitrile: methanol (60:40 v/v) ratio in combination as mobile phase and at the flow rate of 1 ml/minute at λmax 210 nm. Chromatographic separation was performed on Shimadzu SPD-20A, SD-M10 AVP-Shimadzu, an ODS C-18 Kromacil (250 mm × 4.60 mm) column used as stationary phase. The quantitation of Ramipril done by HPLC, parameters studied were retention time, linearity, accuracy, precision, detection limit, quantitation limit and stability.Results: Linear regression analysis data show a good linear relationship between response and concentration in the range of 5-30 µg/ml; detection carried out at λmax210 nm; the linear regression equation for Ramipril was Y=10327x+72877; R²=0.998. The retention time of the Ramipril was 2.910 min. Percent recoveries obtained for Ramipril was 99.58-100.15%. LOD and LOQ value was 0.802µg/ml and 1.4µg/ml for Ramipril respectively.Conclusion: The result suggested that proposed method gives good peak resolution of Ramipril within short analysis time (<10 min) and high percentages of the recovery shown that method is free from interference of excipient present in the formulation. The % RSD of each parameter lies below the limit of 2%, proven the suitability. The statistical analysis proved that the proposed method is precise, accurate, selective and rapid for the HPLC estimation of Ramipril.Keywords: Fast dissolving tablet, Ramipril, Accuracy, HPLC, Linearit

FORMULATION DEVELOPMENT AND EVALUATION OF FAST DISSOLVING TABLET OF RAMIPRIL

Objective: The aim of this study was to prepare fast dissolving tablet of Ramipril by using Sodium starch glycolate, and Crospovidone as superdisintegrants to enhance the dissolution rate and the disintegration rate and evaluated for Pre and Post Compression parameter of the tablet.Methods: Fast dissolving tablet of Ramipril was prepared by direct compression technique. Fast dissolving tablet was evaluated for Pre compression parameter; bulk density, tapped density, Hausner's ratio, angle of repose and Carr's index and post compression parameter; weight variation, thickness, hardness, friability, wetting time, water absorption ratio, disintegration time and dissolution time. The UV-spectrophotometric method has been used for the quantitation of drug release of Ramipril in the Fast dissolving tablet formulation.Results: Pre and post compression parameter were evaluated. Five different batches of tablets, F1 to F5 were prepared. Bulk density and tapped density was found in the range of 0.64-0.85 g/cm3 and 0.68-0.98 g/cm3 simultaneously. The hardness, friability, wetting time, the water absorption ratio, disintegration and dissolution time were found to be acceptable according to the standard limit and compare to all formulations F4 formulation was selected as the promising formulation. All batches of fast dissolving tablet were satisfactory in term of dissolution. The cumulative percentage of drug release of F4 formulation was 90.12% after 12 min compare to other formulation.Conclusion: The result suggested that the dissolution and disintegration of Ramipril have improved considerably in batch F4 formulation as compared to rest of the formulation. The dissolution rate and dissolution rate of Ramipril can be enhanced to a great extent by the direct compression technique with the addition of superdisintegrants

DESIGN, SYNTHESIS, AND EVALUATION OF NEW DERIVATIVE OF 1,2,4-TRIAZOLES FOR ANTIMICROBIAL AND ANTI-INFLAMMATORY ACTIVITY

Objective: The object of the study is to design, synthesize and biological evaluation of isoniazid derived 1,2,4-triazoles compounds.Methods: Isoniazid based 1,2,4-triazoles derivatives have been synthesized by reaction of Isoniazid with carbon disulfide in basic medium (KOH) to form Potassium dithiocarbazinate salt and reaction with hydrazine hydrate converted into 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol. These compounds were reacted with seven different benzaldehyde to form 4-[(substituted phenyl)-methylene]-amino-5-(pyridine-4-yl)-4H-1,2,4-triazol-3-thiol (4). The final compounds were synthesized by reaction with four different acetanilide to form 4-[substituted phenyl)-methylene]-amino-3-(N-substitutedcarboxamidomethylthio)-5-(pyridine-4-yl)-4H-1,2,4-triazoles derivatives. All these compounds were characterized by IR, 1H-NMR, [13]C-NMR and elemental analysis. The antimicrobial activity was determined by the cup plate method. Acute anti-inflammatory activity determined by using carrageenan-induced rat paw edema model.Results: Series PJ-A4, PJ-A7 and PJ-A13 showed more than 90% of the zone of inhibition against both Gram positive and Gram negative organisms. The antifungal study suggested that among synthesized compounds series PJ-A4, A7, A9, A11 and A13 showed more than 90% of zone of inhibition, A2, A10 and A12 shows more than 80% of the zone of inhibition. Anti-inflammatory study data indicate that compounds PJ-A4, PJ-A8, PJ-A9 and PJ-A13 produced 70 to 76% of paw edema inhibition compare to standard drug Ibuprofen which showed 83.3% after 5 h. Conclusion: Results suggested that the isoniazid based 1,2,4-triazole derivatives have significant antibacterial, antifungal and anti-inflammatory activity

Comparative Molecular Field Analysis on 4(3H) Quinazolinone derivatives for the Development of Potential Antimicrobial Agents

Objective: Objective of present paper was to perform comparative Molecular Field Analysis on 4(3H) Quinazolinone derivatives for the Development of Potential Antimicrobial Agents. Method: 4(3H)-quinazolinone is one of the most frequently studied heterocyclic moiety possessing wide range of biological activities. Three dimensional quantitative structure activity analysis (3D QSAR) has been carried out on some already reported 4(3H)-quinazolinone derivatives to explore the structural requirements for antifungal and antibacterial activities. QSAR models were generated with comparative molecular field analysis (CoMFA) using partial least square (PLS) method. CoMFA descriptors were calculated on aligned structures to understand the steric and electrostatic field contribution on the biological activity. Result and Discussion: The generated CoMFA models for antifungal activity showed a cross-validation coefficient (q2) of 0.578, non-cross validation coefficient (r2) of 0.923 and standard error of 0.0177. The predictive ability of the model was validated using external validation with predictive factor (r2pred) of 0.94 for antifungal activity. The significant statistical parameters indicated the reliability and good predictive power of the developed model. The 3D contour maps generated from CoMFA models were analyzed for key structural requirements for improved activity. Conclusion: This study will help to further optimize quinazoline-4(3H)-one derivatives for antimicrobial activities. Keywords: 4(3H)-quinazolinones; 3D QSAR; Comparative molecular field analysis (CoMFA); antifungal activity; antibacterial activity